Comparative Study of Cardiovascular Effects of Selected Pulmonary Vasodilators in Canine Models of Mitral Valve Disease.

Previous reports have shown that various oral pulmonary vasodilators are effective against canine pulmonary hypertension (PH). However, no studies have compared their hemodynamic effects. We aimed to compare the hemodynamic effects of 15 µg/kg beraprost sodium, 1.0 mg/kg sildenafil, and their combination, in dogs with experimentally induced mitral regurgitation. This experimental crossover study evaluated the hemodynamic and functional effects of oral pulmonary vasodilators by application of right-sided heart catheterization and echocardiography. Beraprost significantly decreased pulmonary and systemic vascular resistance. Additionally, beraprost increased right-ventricular stroke volume and left-ventricular cardiac output without worsening left-heart size and left-atrial pressure. The pulmonary vasodilatory effects of sildenafil were stronger, and its systemic vasodilatory effects were weaker than those of beraprost. However, sildenafil significantly increased the left-ventricular volume, left-atrial pressure indicator, and right-ventricular cardiac output. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart size and left-atrial pressure indicators. Both beraprost and sildenafil were effective against canine PH; however, sildenafil was associated with the risk of worsening left-heart loading. Combination therapy with beraprost and sildenafil synergistically dilated pulmonary and systemic vessels, indicating a more potent treatment option for severe PH cases.

Pulmonary thrombotic pulmonary hypertension managed using antithrombotic and pulmonary vasodilator treatment.

An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low-molecular-weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension. On Day 13, contrast-enhanced computed tomography identified extensive contrast defects in the pulmonary arteries, and IV monteplase was administered on Days 14 and 18, with marked improvement in respiratory status and exertional dyspnea on Day 20. Right ventricular function and McConnell signs also improved, and tricuspid regurgitation velocity and pulmonary vascular resistance decreased. On Day 250, echocardiography indicated further improvement in pulmonary hypertension pathophysiology. The patient was still progressing well with antithrombotic and pulmonary vasodilator treatment 400 days later.

Echocardiographic characteristics of dogs with pulmonary hypertension secondary to respiratory diseases.

BACKGROUND: Pulmonary hypertension (PH) secondary to respiratory disease is caused by pulmonary vascular remodeling and hypoxia. Severe PH can induce various clinical signs, including syncope and right-sided heart failure. HYPOTHESIS/OBJECTIVES: To investigate the echocardiographic characteristics in dogs with PH secondary to respiratory diseases. ANIMALS: Thirty-one dogs with respiratory diseases with or without PH and 15 healthy dogs. METHODS: Prospective cross-sectional study. Dogs were classified according to respiratory disease (obstructive airway/lung disease [OALD] or restrictive lung disease [RLD]) and PH-relevant signs. The association between echocardiographic variables and PH (classified by respiratory disease and PH-relevant signs) was investigated. RESULTS: Twenty-one dogs were diagnosed with PH; of these, 11 showed PH-related signs (OALD, n = 2; RLD, n = 9), 14 had right ventricular hypertrophy, and 19 had pulmonary arterial enlargement. Right ventricular dysfunction and dilatation were observed only in dogs with PH-related signs (n = 10). Left and right ventricular stroke volumes were significantly lower in dogs with PH (median [interquartile range]: 17.2 [12.4-20.8] and 16.8 [15.3-29.5] mL/m2 , respectively). Dogs with RLD had higher echocardiography-estimated pulmonary vascular resistance than those with OALD (median [interquartile range]: 3.1 [1.9-3.3] and 1.6 [1.3-2.2], respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Pulmonary arterial enlargement was the most common echocardiographic finding in dogs with PH secondary to respiratory diseases. Right ventricular dysfunction, dilatation, and decreased left and right ventricular stroke volume were significantly associated with the PH-related signs, indicating that comprehensive echocardiography is recommended in dogs with respiratory disease. Restricted lung disease might induce more severe PH than OALD.

Comparative study of myocardial function in cases of feline hypertrophic cardiomyopathy with and without dynamic left-ventricular outflow-tract obstruction.

In recent years, hypertrophic cardiomyopathy (HCM) in cats has become much more common in clinical practice due to improvements in diagnostic techniques and equipment performance. One phenotype is obstructive HCM with left ventricular (LV) outflow tract obstruction (DLVOTO). It has been reported that the presence or absence of DLVOTO does not affect long-term prognosis in cats with HCM. In this study, we evaluated and compared myocardial function in HCM-affected cats with and without DLVOTO using the two-dimensional speckle-tracking echocardiography. LV longitudinal strain of the endocardial, epicardial, and whole layer and LV circumferential strain of the epicardium were significantly decreased in all HCM-affected cats compared to healthy cats. However, these values were not significantly different between those with and without DLVOTO. In contrast, the endocardial and whole layers of LV circumferential strain were only significantly decreased in HCM-affected cats with DLVOTO compared to healthy cats. This could be attributed to the fact that the LV pressure load associated with DLVOTO affected the endocardial myocardium more in the LV endocardial layer, and that lower values of LV endocardial strain lowered the values of LV strain in the whole layer. In conclusion, our results suggest that LV myocardial function may have been more compromised in the HCM-affected cats with DLVOTO.

Cardiovascular Effect of Epoprostenol and Intravenous Cardiac Drugs for Acute Heart Failure on Canine Pulmonary Hypertension.

Pulmonary hypertension (PH) is a life-threatening complication in dogs with cardiopulmonary disease. Epoprostenol is an intravenous pulmonary vasodilator used to treat PH in humans; however, its efficacy in dogs remains unknown. We investigated the cardiovascular effects of epoprostenol and several cardiac agents for acute heart failure in canine models of chronic PH. Six dogs with chronic PH were anesthetized and underwent right heart catheterization and echocardiography before and after infusion of epoprostenol, dobutamine, dopamine and pimobendane. (The drug administration order was the same for all dogs). High-dose epoprostenol (15-20 ng/kg/min) tended to decrease pulmonary arterial pressure (PAP) while significantly decreasing pulmonary and systemic vascular resistance and increasing left and right ventricular (LV and RV, respectively) function. Pimobendan significantly increased LV and RV functions without increasing PAP. Conversely, dobutamine and dopamine significantly increased LV and RV function as well as PAP. This study revealed the efficacy of epoprostenol in treating canine PH through its pulmonary and systemic vasodilating effects. Although catecholamines improve LV and RV function, they might worsen PH pathophysiology, and careful monitoring may be necessary when using these drugs. Pimobendan improved LV and RV function without increasing PAP; however, a stronger vasodilating effect was observed with epoprostenol.

Presence of known feline ALMS1 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy in Japan.

Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats with a suspected genetic origin. Previous studies have identified five HCM-associated variants in three genes (Myosin binding protein C3: MYBPC3 p.A31P, p.A74T, p.R820W; Myosin heavy chain 7: MYH7 p.E1883K; Alstrom syndrome protein 1: ALMS1 p.G3376R). These variants are considered breed-specific, with the exception of MYBPC3 p.A74T, and have rarely been found in other breeds. However, genetic studies on HCM-associated variants across breeds are still insufficient because of population and breed bias caused by differences in genetic background. This study investigates the ubiquitous occurrence of HCM-associated genetic variants among cat breeds, using 57 HCM-affected, 19 HCM-unaffected, and 227 non-examined cats from the Japanese population. Genotyping of the five variants revealed the presence of MYBPC3 p.A31P and ALMS1 p.G3376R in two (Munchkin and Scottish Fold) and five non-specific breeds (American Shorthair, Exotic Shorthair, Minuet, Munchkin and Scottish Fold), respectively, in which the variants had not been identified previously. In addition, our results indicate that the ALMS1 variants identified in the Sphynx breed might not be Sphynx-specific. Overall, our results suggest that these two specific variants may still be found in other cat breeds and should be examined in detail in a population-driven manner. Furthermore, applying genetic testing to Munchkin and Scottish Fold, the breeds with both MYBPC3 and ALMS1 variants, will help prevent the development of new HCM-affected cat colonies.

Prognostic value of pulmonary vascular resistance estimated by echocardiography in dogs with myxomatous mitral valve disease and pulmonary hypertension.

BACKGROUND: Progression to combined post- and pre-capillary pulmonary hypertension (PH) provides prognostic information in human patients with post-capillary PH. Pulmonary vascular resistance estimated by echocardiography (PVRecho) is useful for the stratification of dogs with myxomatous mitral valve disease (MMVD) and detectable tricuspid regurgitation. OBJECTIVES: To evaluate the prognostic value of PVRecho in dogs with MMVD. ANIMALS: Fifty-four dogs with MMVD and detectable tricuspid regurgitation. METHODS: Prospective cohort study. All dogs underwent echocardiography. The PVRecho was calculated based on tricuspid regurgitation and the velocity-time integral of the pulmonary artery flow. To evaluate the influence of echocardiographic variables on cardiac-related deaths, Cox proportional hazard analysis was performed. Additionally, Kaplan-Meier curves classified by PVRecho tertiles were made and compared using log-rank tests to evaluate the influence of PVRecho on all-cause mortality and cardiac-related death. RESULTS: The median follow-up time was 579 days. Forty-one dogs with MMVD (PH severity [number]: no or mild, 21/33; moderate, 11/11; severe, 9/10) died during the study. In the multivariable Cox proportional hazard analysis adjusted for age, sildenafil administration, and American College of Veterinary Internal Medicine stage of MMVD, left atrial to aortic diameter ratio and PVRecho remained significant (adjusted hazard ratio [95% confidence interval]: 1.2 [1.1-1.3] and 2.1 [1.6-3.0], respectively). Higher PVRecho showed a significant association with lower survival rates. CONCLUSIONS AND CLINICAL IMPORTANCE: Left atrial enlargement and high PVRecho were independent prognostic factors in dogs with MMVD and detectable tricuspid regurgitation.

Optimal Intravenous Administration Procedure for Efficient Delivery of Canine Adipose-Derived Mesenchymal Stem Cells.

Mesenchymal stem cells (MSC) are currently being investigated for their therapeutic applications in a wide range of diseases. Although many studies examined peripheral venous administration of MSC, few have investigated the detailed intravenous administration procedures of MSC from their preparation until they enter the body. The current study therefore aimed to explore the most efficient infusion procedure for MSC delivery by preparing and infusing them under various conditions. Canine adipose-derived mesenchymal stem cells (cADSC) were infused using different infusion apparatuses, suspension solutions, allogenic serum supplementation, infusion time and rates, and cell densities, respectively. Live and dead cell counts were then assessed by manual measurements and flow cytometry. Efficiency of live- and dead-cell infusion and cell viability were calculated from the measured cell counts and compared under each condition. Efficiency of live-cell infusion differed significantly according to the infusion apparatus, infusion rate, and combination of cell density and serum supplementation. Cell viability after infusion differed significantly between the infusion apparatuses. The optimal infusion procedure resulting in the highest cell delivery and viability involved suspending cADSC in normal saline supplemented with 5% allogenic serum at a density of 5 × 105 cells/mL, and infusing them using an automatic infusion device for 15 min. This procedure is therefore recommended as the standard procedure for the intravenous administration of ADSC in terms of cell-delivery efficiency.

A Case of a Small-Breed Dog with Diet-Related Dilated Cardiomyopathy Showing Marked Improvements in Cardiac Morphology and Function after Dietary Modification.

An 11-year-old intact female Papillion weighing 2.1 kg was referred to our institution with the main complaint of shallow, rapid breathing. At the first visit (day 0), although clinical signs improved due to the use of medication from the primary hospital, transthoracic radiography and echocardiography revealed left heart enlargement and left ventricular dysfunction. A clinical diagnosis of dilated cardiomyopathy (DCM) was made and oral administration of pimobendan, temocapril, and taurine was initiated. However, on day 10, the respiratory status worsened and furosemide was prescribed. On day 54, no significant improvement in heart size was observed. Additionally, the diet that this patient received met the recommendation for diet-related DCM by the U.S. Food and Drug Administration, and the patient's diet was changed from a grain-free diet to a grain-containing diet. On day 1191, the patient's respiratory status was stable and no clinical signs were observed. Transthoracic radiography and echocardiography revealed an improvement in left heart size. Additionally, improvements in the left and right ventricular myocardial strains were observed after changing the diet. We suggest that it may be necessary to suspect a dietary association with dilated cardiomyopathy, and a good prognosis might be expected by dietary modification, even in small-breed dogs.

Beraprost Sodium for Pulmonary Hypertension in Dogs: Effect on Hemodynamics and Cardiac Function.

Pulmonary hypertension (PH) is a fatal condition that affects many dogs. In humans, PH is often treated with beraprost sodium (BPS). However, the effectiveness of BPS for canine PH has not been established. This study aimed to evaluate the clinical and cardiovascular response of BPS in canine patients with PH of various causes. Sixteen dogs with PH (post-capillary PH, n = 8; pre-capillary PH, n = 8) were included. BPS was continuously administered twice daily at 15 µg/kg. All dogs underwent echocardiography, including speckle-tracking analysis and blood pressure measurement, before and after BPS administration. Continuous BPS administration (range: 13.2-22.0 µg/kg) significantly decreased the pulmonary and systemic vascular impedance and increased left and right ventricular myocardial strain. In dogs with post-capillary PH, BPS administration caused no significant worsening of the left atrial pressure indicators. No side effects of BPS were observed in any dog. BPS also improved cardiac function and pulmonary circulation through pulmonary vasodilation, suggesting that BPS may be an additional treatment option for canine PH of various causes. Particularly, BPS increased left ventricular function and systemic circulation without worsening the left heart loading condition in dogs with post-capillary PH.

Influence of heart rate on right ventricular function assessed by right heart catheterization and echocardiography in healthy anesthetized dogs.

BACKGROUND: Right ventricular (RV) functional assessment has received considerable attention in veterinary medicine since various diseases, such as cardiovascular, respiratory, endocrine, and neoplastic disease, may affect RV function. Heart rate (HR) is an important factor that can influence RV function through changes in loading condition and contractility. However, no study has yet evaluated the association between HR and RV function in the same individuals. This study aimed to evaluate the influence of elevated HR on RV function using right heart catheterization and echocardiography, and investigate the association between right heart catheterization and echocardiographic indices. RESULTS: Right atrial pacing was performed in eight dogs at 120, 140, 160, and 180 bpm. With an increase in HR, the RV systolic volume, RV diastolic volume, and stroke volume significantly decreased; however, the cardiac output, end-systolic elastance (Ees), and effective arterial elastance (Ea) significantly increased. Significant changes were not observed in RV pressure and Ees/Ea. The RV area normalized by body weight, RV fractional area change normalized by body weight (RV FACn), and tricuspid annular plane systolic excursion normalized by body weight (TAPSEn) significantly decreased with increased HR. Peak systolic myocardial velocity of the lateral tricuspid annulus (RV s'), RV strain, and RV strain rate of only the RV free wall analysis (RV-SrL3seg) showed no significant changes with the increase in HR; however, there was an increase in the RV strain rate of the RV global analysis (RV-SrL6seg). Multiple regression analysis revealed that HR, RV FACn, and RV- SrL6seg had significant associations with the Ees, and the TAPSEn and RV-SrL3seg with Ees/Ea. CONCLUSIONS: Decreased venous return and shortened relaxation time decreased the RV FAC, TAPSE, RV s', and RV strain, and might underestimate the RV function. Ees increased with the increase in HR, reflecting the myocardial force-frequency relation; as a result, RV-SrL6seg could be a useful tool for Ees estimation. Additionally, the RV-SrL3seg could detect RV performance, reflecting the balance between RV contractility and RV afterload.

Investigation of Beraprost Sodium on Cardiac Function and Hemodynamics in Canine Models of Chronic Pulmonary Hypertension.

Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by increased pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. No study has evaluated the utility of Beraprost sodium (BPS) in dogs with PH. This study aimed to evaluate the effect of BPS on cardiac function and hemodynamics and examine the optimal dose of BPS in canine models of chronic embolic PH. In this prospective crossover study, three doses of BPS (5, 15, and 25 µg/kg, twice a day) were examined in eight canine models of chronic embolic PH. All model dogs underwent invasive PAP measurement, echocardiography, and non-invasive systemic blood pressure measurement before and after continuous administration of oral BPS for 1 week. No side effects of BPS were observed in any dog during the study. All doses of BPS significantly decreased systolic PAP and pulmonary vascular impedance. Additionally, systemic vascular impedance significantly decreased with 15 and 25 µg/kg of BPS. The right ventricular stroke volume and longitudinal strain significantly decreased with all doses of BPS. The left ventricular stroke volume and circumferential strain decreased with 15 µg/kg BPS. BPS was well-tolerated in this study. A dose-dependent vasodilating effect on pulmonary vessels was observed in canine models of chronic PH. Additionally, 15 µg/kg BPS showed a balanced vasodilating effect on systemic and pulmonary vessels. Furthermore, with a decrease in systemic and pulmonary vascular impedance, the left and right ventricular functions were significantly improved. Our results suggest that BPS may be useful in the treatment of canine PH.

Utility of Real-Time Three-Dimensional Echocardiography for the Assessment of Right Ventricular Morphology and Function in Large Animal Models.

Real-time three-dimensional echocardiography (RT3DE) enables a noninvasive assessment of right ventricular (RV) morphology. However, no study has evaluated the relationship between RV function obtained by RT3DE and RV pressure-volume loops. This hypothesis-driven, experimental study aimed to assess the utility of RT3DE in the evaluation of RV morphology and function. Ten anesthetized beagle dogs sequentially underwent dobutamine infusion, acute infusion of lactated Ringer's solution, and furosemide administration to alter RV contractility and loading conditions. RV pressure-volume loop-derived hemodynamic measurements and echocardiography, including two-dimensional speckle-tracking echocardiography and RT3DE, were performed in each study protocol. Bland−Altman analysis showed strong agreement in RV volume, ejection fraction, and stroke volume obtained by right heart catheterization and RT3DE. Multiple regression analyses revealed that the peak myocardial velocity of the lateral tricuspid annulus (RV s') and global RV longitudinal strain rate were significantly associated with end-systolic elastance (adjusted r2 = 0.66, p < 0.001). RV s', RV free wall longitudinal strain, and RT3DE-derived stroke volume/end-systolic RV volume ratio were associated with RV pressure-volume loops-derived end-systolic/arterial elastance ratio (adjusted r2 = 0.34, p < 0.001). RT3DE could detect the changes in catheterization-derived RV volume with a strong agreement and might be useful in estimating RV-pulmonary arterial coupling.

Detection of Congestive Heart Failure and Myocardial Dysfunction in Cats With Cardiomyopathy by Using Two-Dimensional Speckle-Tracking Echocardiography.

Congestive heart failure (CHF) is a life-threatening condition in cats with cardiomyopathy. We hypothesized that myocardial dysfunction may induce progression to CHF pathophysiology in cats with cardiomyopathy. However, no previous studies have evaluated the involvement of myocardial dysfunction in cats with CHF. In this study, we aimed to evaluate the relationship between CHF and myocardial function assessed using two-dimensional speckle-tracking echocardiography (2D-STE). Sixteen client-owned healthy cats and 32 cats with cardiomyopathy were enrolled in this study. Cats were classified into three groups: healthy cats, cardiomyopathy without CHF (CM group), and cardiomyopathy with CHF (CHF group). Left ventricular (LV) longitudinal and circumferential strains (SL and SC, respectively), and right ventricular (RV) SL were measured using 2D-STE. Logistic regression analysis was performed to assess the relationship between CHF and echocardiographic variables, including 2D-STE. Results comparing the healthy cats and CM vs. CHF groups showed that increased left atrial to aortic diameter ratio and decreased LV apical SC were significantly associated with the existence of CHF (odds ratio [95% confidence interval]: 1.40 [1.16-1.78] and 1.59 [1.06-2.36], respectively). Results comparing the CM vs. CHF group showed that increased end-diastolic RV internal dimension and decreased RV SL were significantly associated with the existence of CHF (odds ratio: 1.07 [1.00-1.13] and 1.34 [1.07-1.68], respectively). Left atrial enlargement and depressed LV apical myocardial function may be useful tools for predicting the progression to CHF in cats. Furthermore, RV enlargement and dysfunction may lead to the onset of CHF in asymptomatic cats with cardiomyopathy.

Pulmonary Vascular Resistance Estimated by Echocardiography in Dogs With Myxomatous Mitral Valve Disease and Pulmonary Hypertension Probability.

Post-capillary pulmonary hypertension (PH) is a life-threatening complication in dogs with myxomatous mitral valve disease (MMVD). An increase in pulmonary vascular resistance (PVR) is associated with post-capillary PH progression. In humans, PVR estimated by echocardiography (PVRecho) enables the non-invasive assessment of PVR in patients with PH. This study aimed to evaluate the clinical utility of PVRecho in dogs with MMVD, PH probability, and right-sided congestive heart failure (R-CHF). Dogs with MMVD and detectable tricuspid valve regurgitation were included in the study. Dogs were classified into three PH probability groups (low/intermediate/high) and according to the presence or absence of R-CHF. All dogs underwent echocardiographic measurements for right ventricular (RV) morphology and function. PVRecho was calculated by two methods using tricuspid valve regurgitation velocity and velocity-time integral of the pulmonary artery flow (PVRecho and PVRecho2). RV size indicators were significantly higher with a higher probability of PH. RV strain and velocity-time integral of the pulmonary artery flow in the high probability group were significantly lower than those in the other groups. Tricuspid valve regurgitation velocity, PVRecho, and PVRecho2 were significantly higher with an increase in PH probability. Logistic regression analysis revealed a significant association between the presence of R-CHF and increased PVRecho2 and end-diastolic RV internal dimension normalized by body weight. PVRecho and PVRecho2 showed significant differences among the PH probability groups. These non-invasive variables may be useful for the diagnosis and stratification of PH and the determination of the presence of R-CHF in dogs with MMVD.

Right ventricular systolic and diastolic function assessed by two-dimensional speckle tracking echocardiography in dogs with myxomatous mitral valve disease.

Pulmonary hypertension (PH) is a common comorbidity in dogs with myxomatous mitral valve disease (MMVD), and can induce various changes in the right heart, such as right ventricular (RV) hypertrophy, dilatation, and dysfunction. We hypothesized that RV function, not only systolic function but also diastolic function, could be worsened with PH progression. We aimed to compare RV systolic and diastolic function in dogs with MMVD. Twenty healthy dogs and sixty-eight dogs with MMVD were enrolled. Dogs with MMVD were classified into the probability of PH. Two-dimensional and Doppler echocardiographic indices for right heart and two-dimensional speckle tracking echocardiography indices were measured. The morphological indicators of the right heart were significantly higher only in the high probability of PH group. The RV strain, early-diastolic and systolic strain rates were significantly lower in the high probability of PH group than those in the low and intermediate probability of PH groups. Multivariate analysis showed that increased RV internal dimension normalized by body weight and RV myocardial performance index were significantly associated with the presence of right-sided congestive heart failure. Speckle tracking echocardiography-derived RV systolic and diastolic function were activated in the low and intermediate probability of PH groups. However, dogs with high probability of PH showed RV myocardial dysfunction and dilatation. Increased RV myocardial performance index and end-diastolic RV internal dimension normalized by body weight were significantly associated with the presence of right-sided congestive heart failure in dogs with MMVD.

Investigation of the influence of manual ventilation-controlled respiration on right ventricular pressure-volume loops and echocardiographic variables in healthy anesthetized dogs.

OBJECTIVE: To evaluate the influence of manual ventilation-controlled respiration on right ventricular (RV) pressure-volume loop-derived and echocardiographic variables in dogs. ANIMALS: 8 healthy, anesthetized Beagles. PROCEDURES: In a prospective experimental study, pressure-volume catheters were percutaneously inserted into the right ventricle of each dog, and manual ventilation was performed; RV pressure-volume loop (hemodynamic) data and conventional echocardiographic variables were assessed. Two-dimensional speckle tracking echocardiography-derived RV strain (RVS) and RV systolic strain rate (RVSR) were obtained with RV free wall-only analysis (free wall) and RV global analysis (RVGA; interventricular septum). Variables were compared between end-inspiratory and end-expiratory phases of respiration by statistical methods. Multiple regression analysis was used to assess associations between selected hemodynamic and echocardiographic variables. RESULTS: The RV pressure significantly increased, and RV volume, stroke volume, tricuspid annular plane systolic excursion, RV fractional area change, peak myocardial systolic velocity of the lateral tricuspid annulus, and RV free wall only-assessed RVS and RVSR significantly decreased in the inspiratory phase, compared with the expiratory phase. There were no significant differences in end-systolic elastance or RVGA-assessed RVS or RVSR between respiratory phases. The RVGA-assessed RVSR was significantly associated with stroke volume and end-systolic elastance. CONCLUSIONS AND CLINICAL RELEVANCE: Specific RV echocardiographic variables were significantly affected by respiration. In contrast, RVS and RVSR determined with RVGA were not affected by respiration and were associated with hemodynamic indicators of RV contractility.

Right Ventricular Myocardial Adaptation Assessed by Two-Dimensional Speckle Tracking Echocardiography in Canine Models of Chronic Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by an increase in pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. Right ventricle adapts to its pressure overload through various right ventricular (RV) compensative mechanisms: adaptive and maladaptive remodeling. The former is characterized by concentric hypertrophy and increased compensatory myocardial contractility, whereas the latter is distinguished by eccentric hypertrophy associated with impaired myocardial function. Objectives: To evaluate the RV adaptation associated with the increase of PAP using two-dimensional speckle tracking echocardiography. Animals: Seven experimentally induced PH models. Methods: Dogs were anesthetized and then a pulmonary artery catheter was placed via the right jugular vein. Canine models of PH were induced by the repeated injection of microspheres through the catheter and monitored pulmonary artery pressure. Dogs were performed echocardiography and hemodynamic measurements in a conscious state when baseline and systolic PAP (sPAP) rose to 30, 40, 50 mmHg, and chronic phase. The chronic phase was defined that the sPAP was maintained at 50 mmHg or more for 4 weeks without injection of microspheres. Results: Pulmonary artery to aortic diameter ratio, RV area, end-diastolic RV wall thickness, and RV myocardial performance index were significantly increased in the chronic phase compared with that in the baseline. Tricuspid annular plane systolic excursion was significantly decreased in the chronic phase compared with that in the baseline. The RV longitudinal strain was significantly decreased in the sPAP30 phase, increased in the sPAP40 and sPAP50 phases, and decreased in the chronic phase. Conclusions: Changes in two-dimensional speckle tracking echocardiography-derived RV longitudinal strain might reflect the intrinsic RV myocardial contractility during the PH progression, which could not be detected by conventional echocardiographic parameters.

Early detection of myocardial dysfunction in a cat that gradually progressed to endomyocardial form of restrictive cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is a common myocardial disease in cats, characterized by diastolic dysfunction and atrial enlargement without myocardial hypertrophy. Especially, endomyocardial form of RCM, one of the subtypes in RCM, is characterized by endocardial fibrosis, endocardial scar bridging the interventricular septum and left ventricular (LV) free wall, and deformation and distortion of the LV. However, it is unclear how the myocardial dysfunction and the endocardial scar contribute to the pathophysiology of RCM disease progression. CASE PRESENTATION: A 3 years and 2 months old, intact male, Domestic shorthaired cat was presented for consultation of cardiac murmur. At the first visit (day 0), the notable abnormal finding was echocardiography-derived chordae tendineae-like structure bridging the interventricular septum and the LV free wall, resulting high-speed blood flow in the left ventricle. Electrocardiography, thoracic radiography and noninvasive blood pressure measurements were normal. No left atrial enlargement was observed, and LV inflow velocity showed an abnormal relaxation pattern. Although there was no abnormality in tissue Doppler imaging-derived myocardial velocity, two-dimensional speckle tracking echocardiography (2D-STE) revealed a decrease in the LV longitudinal strain and an increase in endocardial to epicardial ratio of the LV circumferential strain on day 0. On day 468, obvious left atrium enlargement and smoke like echo in the left atrium were observed. The LV inflow velocity was fused, and the tissue Doppler imaging-derived early-diastolic myocardial velocity of the septal mitral annulus decreased. Regarding 2D-STE, LV circumferential strain was further decreased, and right ventricular strain was additionally decreased. Although the general condition was good, we made a clinical diagnosis of endomyocardial RCM based on the above findings. On day 503, the cat showed the radiographic evidence of pulmonary edema and congestive heart failure signs. CONCLUSIONS: Cats with abnormal LV structure and associated myocardial dysfunction like this case needs careful observation. Additionally, 2D-STE indices may be useful for early detection of myocardial dysfunction in feline RCM.

Immunomodulatory Effects of Canine Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles on Stimulated CD4+ T Cells Isolated from Peripheral Blood Mononuclear Cells.

Adipose tissue-derived mesenchymal stem cells (ADSCs) have anti-inflammatory and immunomodulatory characteristics. Many studies have suggested that the immunomodulation of ADSCs is largely mediated by secreted paracrine factors. Various factors are secreted from ADSCs, among which extracellular vesicles are considered to play a major role in the communication between ADSCs and target cells. Several studies have reported the function of canine ADSC-derived extracellular vesicles (cADSC-EVs), but few studies have reported the immunomodulatory effects of cADSC-EVs on immune cells. The purpose of this study was to investigate the effects of cADSC-EVs on in vitro-stimulated CD4+ T cells isolated from peripheral blood mononuclear cells (PBMCs). cADSC-EVs were isolated from cADSCs under naive conditions or primed conditions by tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ). The expression levels of several microRNAs in cADSC-EVs were altered by priming with TNFα and IFNγ. Culturing PBMCs stimulated with concanavalin A in the presence of naive or primed cADSC-EVs inhibited the differentiation of PBMCs and CD4+ T cells and promoted apoptosis of PBMCs. CD4+, CD8+, and CD4+CD8+ T cells were decreased, while CD3+CD4-CD8- T cells were increased. T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells were analyzed by flow cytometry. cADSC-EVs inhibited the proliferation of Th1 and Th17 cells and enhanced Th2 and Treg cell proliferation. However, CD4+ T cells that had incorporated labeled cADSC-EVs comprised only a few percent of all cells. Therefore, these responses of stimulated CD4+ T cells may be due to not only direct effects of cADSC-EVs but also to indirect effects through interactions between cADSC-EVs and other immune cells. In conclusion, cADSC-EVs exert immunosuppressive effects on stimulated CD4+ T cells in vitro. These findings may be useful for further studies of immune diseases.